tbuckley/cabot-search huggingface dataset:
Birth incidence and outcome of harlequin ichthyosis and collodion membrane in the UK and Ireland: a national 2-year prospective surveillance study
Authors: Celia Moss, Fozia Roked, Peter J Davis, Murtaza Khan, Catherine Tyler, Samantha Ibbs, Andrew K Ewer
Journal: British Journal of Dermatology (2022)

Collodion membrane covers a heterogeneous group of ichthyoses with disparate outcomes. In this large, prospective birth-cohort study we show that babies with non-syndromic collodion membrane are born in good condition and in 40% the ichthyosis resolves within a year. Our data challenges existing guidelines and supports expectant management.
A homozygous p.Leu813Pro gain-of-function <i>NLRP1</i> variant causes phenotypes of different severity in two siblings
Authors: Mingfeng Li, Kenneth Lay, Andreas Zimmer, Kristin Technau-Hafsi, Jasmine Wong, Antonia Reimer-Taschenbrecker, Jan Rohr, Ebtesam Abdalla, Judith Fischer, Bruno Reversade, Cristina Has
Journal: British Journal of Dermatology (2022)

Abstract Background A trio exome sequencing study identified a previously unreported NLRP1 gene variant resulting in a p.Leu813Pro substitution of the LRR (leucine-rich repeats) domain of the NLRP1 protein (NACHT, LRR and PYD domains-containing protein 1). This homozygous mutation was shared by two sisters with different clinical presentation: the younger sister had generalized inflammatory nodules with keratotic plugs, clinically resembling multiple keratoacanthomas, while the older had manifestations of familial keratosis lichenoides chronica. Objectives To analyse the consequences of this NLRP1 variant in two siblings with a different clinical spectrum of severity. Methods To demonstrate the pathogenicity, p.Leu813Pro was recombinantly expressed, and its effect on inflammasome assembly was assessed. Exome sequencing and RNA-Seq were performed to identify factors with potentially modifying effects on the severity of the skin manifestation between each sibling. Results The variant p.Leu813Pro triggered activation of the NLRP1 inflammasome leading to ASC (apoptosis-associated speck-like protein containing a CARD) speck formation and interleukin (IL)-1β release. The more severely affected sister had several additional genomic variants associated with atopy and psoriasis that were not present in her sibling. IL-5 and IL-17 emerged as dominant cytokines driving prominent inflammation in the skin of the severely affected sibling. Conclusions To the best of our knowledge, this is the first report of a NLRP1 variant that leads to a different clinical spectrum of severity within the same sibship. IL-5 and IL-17 were the main cytokines expressed in the inflammatory lesions of the severely affected patient and might be regarded as disease modifying factors, and therefore may be considered as therapeutic targets.
Pigmented demodicosis presenting as lentigo maligna diagnosed by reflectance confocal microscopy
Authors: Clemence Bertold, Philippe Martel, Thierry Passeron, Philippe Bahadoran
Journal: British Journal of Dermatology (2023)

The differential diagnosis between benign pigmented macules and lentigo maligna (LM) is clinically challenging. The presence of pigmented circles around hair follicles is an important dermoscopic clue for the diagnosis of LM. Here we report on a woman with a pigmented macule of the face with perifollicular circles for whom the diagnosis of LM was suspected. Instead, reflectance confocal microscopy diagnosed pigmented demodicosis, spared an unnecessary biopsy, and deciphered the mechanisms of hyperpigmentation.
Successful treatment of vitiligo with crisaborole ointment: a report of two cases
Authors: Xiukun Sun, Anqi Sheng, Ai-e Xu
Journal: British Journal of Dermatology (2022)

As selective PDE-4 small molecule inhibitor, Crisaborole has been used with success in atopic dermatitis and psoriasis. Here we report two vitiligo patients successfully treated with crisaborole ointment.
Interleukin-13 inhibition by tralokinumab reduces inducible T-cell costimulator-positive innate lymphoid cells in skin lesions of atopic dermatitis
Authors: Toshiaki Kogame, Satoru Yonekura, Paola Lovato, Masahiro Hirata, Riko Takimoto-ito, Tomoya Takegami, Takayoshi Komatsu-Fujii, Naotomo Kambe, Takashi Nomura, Mads A Røpke, Kenji Kabashima
Journal: British Journal of Dermatology (2022)

Despite the low frequency of skin ILCs and the limited number of samples analyzed in this study, our data indicate that ICOS+ ILCs express IL-13Rα1 and that the density of ICOS+ ILCs decreased four weeks after initiation of treatment with tralokinumab.
Pain experiences among those living with hidradenitis suppurativa: a qualitative study
Authors: Lauren A V Orenstein, Nicole Salame, Meron R Siira, Megan Urbanski, Nyla I Flowers, Harika Echuri, Amit Garg, Anne Marie McKenzie-Brown, Kimberly A Curseen, Rachel E Patzer, Dio Kavalieratos, Suephy C Chen
Journal: British Journal of Dermatology (2022)

Abstract Background Pain is rated by patients with hidradenitis suppurativa (HS) as the disease’s most impactful symptom. HS therapies are often insufficient to control inflammatory disease activity and pain. A better understanding of patient experiences with pain may improve patient–provider relationships and help identify strategies for addressing HS pain. Objectives This qualitative study sought to characterize lived pain experiences of those with HS. Methods English-speaking patients ≥ 18 years old with a dermatologist-confirmed diagnosis of HS and an average numerical rating scale pain score of ≥ 1 over the preceding week were recruited from a single academic medical centre in Atlanta, Georgia, USA. Semistructured interviews were conducted from November 2019 to March 2020 to explore participants’ HS pain experiences and the subsequent impact on their lives. Thematic saturation was reached after interviewing 21 participants. Interviews were audio recorded, transcribed, and analysed using thematic analysis. Results Among 21 study participants, the median 7-day average pain score was 6 (interquartile range 3–7; scale ranges from 0 to 10, with 10 being most pain). Participants’ descriptions of pain were consistent with nociceptive pain, neuropathic pain and itch. Pain impacted multiple life domains, including physical limitations (decreased mobility and impaired sleep), decreased psychological wellbeing (irritability, depression, loss of control, and difficulty communicating pain experiences) and impaired social relationships (social isolation, intimacy problems and difficulty fulfilling social responsibilities). Although participants reported chronic discomfort, acutely painful and unpredictable HS disease flares caused more distress and quality-of-life (QoL) burden. Participants frequently treated their pain without input from the medical team, sometimes with unsafe medication doses or combinations. Factors contributing to self-management of pain included difficulty accessing timely outpatient care during disease flares and fear of stigma from healthcare providers. Conclusions When present, HS-related pain may impact not only physical wellbeing but also mental health and relationships. In addition to therapies that target the inflammatory disease burden, treating the symptom of pain may improve patients’ QoL and wellbeing. Because patients with HS have difficulty explaining their pain, proactively asking them about pain may identify unmet needs, facilitate better pain control and improve QoL. Further, the influence of HS-related pain on numerous aspects of QoL suggests the need for multidisciplinary, patient-centred approaches to HS pain management.
Clinical research: photo validation study using Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) scores in patients with dermatomyositis
Authors: Madison Grinnell, Josef Concha, Rui Feng, Emily Keyes, Joyce Okawa, DeAnna Diaz, Thomas Vazquez, Victoria P Werth
Journal: British Journal of Dermatology (2022)

In this study, we evaluated Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) scores calculated from photos taken by trained clinic staff. We found excellent reliability between photographs and an in-person scoring of the CDASI activity portion in patients with dermatomyositis although the CDASI may be underestimated from photographs. More research is needed to determine if photographs taken outside the office setting may be used to assess clinical trials outcomes.
B-cell-derived transforming growth factor-β may drive the activation of inflammatory macrophages and contribute to scarring in hidradenitis suppurativa
Authors: Conor M Smith, Roisin Hambly, Solene Gatault, Luis F Iglesias-Martinez, Sean Kearns, Helen Rea, Vivien Marasigan, Kate Lynam-Loane, Shivashini Kirthi, Rosalind Hughes, Jean M Fletcher, Walter Kolch, Brian Kirby
Journal: British Journal of Dermatology (2022)

Lesional HS skin was analysed using RNA-sequencing to assess the predicted functional interplay between B cells and macrophages. Our findings support the idea that TGF-beta plays a key role in HS pathogenesis. It is likely that the development of tunnels and scarring in HS is closely related to a chronic activation of TGF-beta signalling.
Biallelic <i>TUFT1</i> variants cause woolly hair, superficial skin fragility and desmosomal defects
Authors: Adam Jackson, Celia Moss, Kate E Chandler, Pablo Lopez Balboa, Maria L Bageta, Gabriela Petrof, Anna E Martinez, Lu Liu, Alyson Guy, Jemima E Mellerio, John Y W Lee, Malobi Ogboli, Gavin Ryan, John A McGrath, Siddharth Banka
Journal: British Journal of Dermatology (2022)

Abstract Background Desmosomes are complex cell junction structures that connect intermediate filaments providing strong cell-to-cell adhesion in tissues exposed to mechanical stress. Objectives To identify causal variants in individuals with woolly hair and skin fragility of unknown genetic cause. Methods This research was conducted using whole-genome sequencing, whole-exome sequencing, clinical phenotyping, haplotype analysis, single-cell RNA sequencing data analysis, immunofluorescence microscopy and transmission electron microscopy. Results We identified homozygous predicted loss-of-function tuftelin-1 (TUFT1) variants in nine individuals, from three families, with woolly hair and skin fragility. One donor splice-site variant, c.60+1G&amp;gt;A, was present in two families, while a frameshift variant, p.Gln189Asnfs*49, was found in the third family. Haplotype analysis showed the c.60+1G&amp;gt;A substitution to be a founder variant in the Irish population that likely arose approximately 20 generations ago. Human and mouse single-cell RNA sequencing data showed TUFT1 expression to be enriched in the hair dermal sheath and keratinocytes. TUFT1 expression was highly correlated with genes encoding desmosomal components implicated in diseases with phenotypes that overlap with the cohort presented here. Immunofluorescence showed tuftelin-1 to be mainly localized to the peripheral cell membranes of keratinocytes in normal skin. Skin samples from individuals with TUFT1 variants showed markedly reduced immunoreactivity for tuftelin-1, with a loss of the keratinocyte cell membrane labelling. Light microscopy revealed keratinocyte adhesion, mild hyperkeratosis and areas of superficial peeling. Transmission electron microscopy showed panepidermal acantholysis with widening of intercellular spaces throughout the epidermis and desmosomal detachment through the inner plaques. Conclusions Biallelic loss-of-function TUFT1 variants cause a new autosomal recessive skin/hair disorder characterized by woolly hair texture and early-onset skin fragility. Tuftelin-1 has a role in desmosomal integrity and function.
Psoriasis and fatigue: a cross-sectional population study of psoriasis patients in the United States using the Medical Expenditure Panel Surveys
Authors: Caterina Zagona-Prizio, Sabrina Khan, Danielle K Yee, Samiya Khan, Nicole Maynard, Rasika Reddy, Manan D Mehta, April W Armstrong
Journal: British Journal of Dermatology (2022)
The impact of hidradenitis suppurativa on professional life
Authors: Sylke Schneider-Burrus, Stefanie Kalus, Björn Fritz, Kerstin Wolk, Susana Gomis-Kleindienst, Robert Sabat
Journal: British Journal of Dermatology (2022)

Abstract Background Hidradenitis suppurativa (HS) is a chronic inflammatory disease that affects intertriginous skin. Objectives To determine the extent of work ability and productivity impairment as a result of HS in Germany. Methods A prospective, multicentre, epidemiological, noninterventional study of patients with HS was conducted. Medical history, medical examination performed by dermatologists and patient-reported outcomes [Work Ability Index (WAI) and Work Productivity and Activity Impairment (WPAI)] were collected. Results Of the 481 patients with HS included in the study, 99% were below the current statutory retirement age. In total, 53·3% of patients were working full time, 16·8% part time and 7·3% had retired. The unemployment rate was 12·6%, two times higher than in the general German population. Medical leave because of HS, within the last 6 months, was reported in 41·4% [95% confidence interval (CI) 36·9–46·0], with a duration of 39·3 days on average (95% CI 32·4–46·1). The mean HS-related WPAI absenteeism was 13.3% (95% CI 9·7–16·8), and the loss in productivity because of HS during working hours (WPAI presenteeism) was 25.2% (95% CI 21·8–28·6). Presenteeism was associated with HS disease severity. Overall work impairment because of HS was 33·4% (95% CI 29·3–37·6). The WAI score for patients was 32·2, ∼20% lower than for the average German employee. Only 62·8% of patients were relatively certain that they would be able to perform their work in the coming 2 years. Being more depressed and having more severe pain were associated with lower work ability and overall work impairment. The estimated annual loss of gross value added because of HS for Germany was ∼€12.6 billion (€3.3 billion related to a lower employment rate, €3.5 billion related to absenteeism and €5.8 billion related to presenteeism). Conclusions HS leads to a substantial decrease in work ability and productivity and considerable loss of gross value added. Impairment during working hours correlates with disease severity, underlining the socioeconomic importance of early and adequate treatment. Furthermore, decreased work ability and productivity is linked to depressed mood and severe pain, aspects that need more attention in patient care.
<i>Strongyloides</i> screening prior to dupilumab therapy in atopic dermatitis: a retrospective cohort study evaluating screening utility
Authors: Kyra Gill, Jennifer Xu, Emily Kozera, Thomas Stewart, Akshay Flora, John W Frew
Journal: British Journal of Dermatology (2022)

The utility of Strongyloidiasis screening in the setting of Dupilumab therapy is unknown. Our retrospective cohort study identifies a low prevalence of Strongyloidiasis with no cases of disseminated disease in the setting of Dupilumab therapy. Baseline IgE and Eosinophil levels were not associated with Strongyloidiasis and screening is likely of low utility.
Is vaccination against COVID-19 associated with psoriasis or eczema flare? Self-controlled case series analysis using data from the Clinical Practice Research Datalink (Aurum)
Authors: Laura Adams, Georgina Nakafero, Matthew J Grainge, Tim Card, Christian D Mallen, Jonathan S Nguyen Van-Tam, Hywel C Williams, Abhishek Abhishek
Journal: British Journal of Dermatology (2022)
Biologic tapering for patients with psoriasis with low disease activity: data from the French PsoBioTeq Registry
Authors: Helene Aubert, Hugo Arlegui, Yann De Rycke, Herve Bachelez, Marie Beylot-Barry, Alain Dupuy, Pascal Joly, Denis Jullien, Emmanuel Mahé, Carle Paul, Marie-Aleth Richard, Emilie Sbidian, Manuelle Viguier, Olivier Chosidow, Florence Tubach, Nathalie Bénéton
Journal: British Journal of Dermatology (2022)

Dose tapering strategies with biologics in psoriasis may lower the treatment burden over time, while enabling high therapeutic response maintenance in patients benefiting from them. Our results should contribute to developing clinical guidelines to fill the current gap in knowledge on this promising therapeutic approach
Efficacy and safety of Oleogel-S10 (birch triterpenes) for epidermolysis bullosa: results from the phase III randomized double-blind phase of the EASE study
Authors: Johannes S Kern, Eli Sprecher, Maria Florencia Fernandez, Franziska Schauer, Christine  Bodemer, Tracy Cunningham, Sandra Löwe, Charles Davis, Mark Sumeray, Anna L Bruckner, Dédée F Murrell
Journal: British Journal of Dermatology (2022)

Epidermolysis bullosa (EB) is a heterogeneous group of rare, difficult-to-treat, inherited multisystem diseases affecting epithelial integrity. Patients with EB are affected by mechanical fragility of epithelial surfaces including the skin and, as a result, extensive recurrent blistering is a characteristic of the condition. Chronic wounds predispose patients with EB to the development of squamous cell carcinoma, which is a major cause of premature death.EASE was a double-blind, randomized, vehicle-controlled, phase III study to determine the efficacy and safety of the topical gel Oleogel-S10 (birch triterpenes) in EB. EASE was funded by Amryt Research Limited.Patients with dystrophic EB, junctional EB or Kindler EB and a target partial-thickness wound lasting ≥ 21 days and < 9 months that was 10-50 cm2, were enrolled and randomized via computer-generated allocation tables 1 : 1 to Oleogel-S10 or control gel - both with standard-of-care dressings. Study gel was applied to all wounds at least every 4 days. The primary endpoint was the proportion of patients with first complete closure of target wound within 45 days.A total of 223 patients were enrolled and treated (109 treated with Oleogel-S10, 114 with control gel). The primary endpoint was met; Oleogel-S10 resulted in 41·3% of patients with first complete target wound closure within 45 days, compared with 28·9% in the control gel arm (relative risk 1·44, 95% confidence interval (CI) 1·01-2·05; P = 0·013). Adverse events (AEs) occurred with similar frequency for Oleogel-S10 (81·7%) compared with control gel (80·7%). AEs were predominantly of mild-to-moderate intensity (4·6% were severe).Oleogel-S10 is the first therapy to demonstrate accelerated wound healing in EB. Oleogel-S10 was well -tolerated.
Impact of response patterns for patients with advanced acral melanoma treated with anti-programmed death-1 monotherapy
Authors: Li Zhou, Lizhi Shao, Shunyu Gao, Chuanliang Cui, Zhihong Chi, Xinan Sheng, Bixia Tang, Lili Mao, Bin Lian, Xieqiao Yan, Xuan Wang, Xue Bai, Siming Li, Jun Guo, Lu Si
Journal: British Journal of Dermatology (2022)

Acral melanoma (AM) is less responsive to immunotherapy than nonacral cutaneous melanoma. Variable responses are seen during immunotherapy, including pseudoprogression, hyperprogressive disease (HPD) and heterogeneous responses. There are currently no studies on the response patterns of patients with AM treated with immunotherapy and the impact on the outcome.To evaluate the response patterns and prognosis of patients with AM treated with anti-programmed death (PD)-1 antibodies.Patients with advanced AM treated prospectively in five clinical trials of anti-PD-1 monotherapy at Peking University Cancer Hospital were included. Responses of individual metastases and heterogeneous responses were evaluated during immunotherapy. Cox proportional hazards regression analysis was conducted to identify the possible predictive factors and generate a nomogram to predict the risk of 1-year and 2-year mortality.The overall response rate was 18·0%, the disease control rate was 36·1%, median progression-free survival was 3·5 months [95% confidence interval (CI) 1·7-5·3] and median overall survival was 17·5 months (95% CI 15·1-19·9) for anti-PD-1 monotherapy. Overall, 9·8% of patients met the criteria of HPD, and displayed a dramatically worse outcome than patients without HPD. In total, 369 metastatic lesions were assessed, with the highest response rate in lymph nodes (20·4%) and the lowest in the liver (5·6%). Homogeneous response, heterogeneous response and heterogeneous or homogeneous progression had different prognoses from the best to the worst. A predictive model was constructed and achieved good accuracy with a C-index of 0·73 (95% CI 0·63-0·84) in the training set and 0·74 (95% CI 0·61-0·86) in the validation set.HPD during immunotherapy serves as an essential biomarker of poor prognosis in advanced AM. Metastases in different sites respond distinctively to immunotherapy. Clinically heterogeneous responses to immunotherapy affect the outcome of patients. A predictive model was built to distinguish the prognosis of acral melanoma under immunotherapy.
The top 10 research priorities for skin cancer surgery in the UK: results of a James Lind Alliance Priority Setting Partnership
Authors: Alistair C Brown, Eleanor M Earp, David Veitch, Aaron Wernham, Rachel Abbott, Jonathan Batchelor, Stuart Belshaw, Kash Bhatti, John Bladen, Alistair Brown, Diane Cannon, Eric Deeson, Eric Dooher, Nigel Dunford, Eleanor Earp, Patricia Fairbrother, Claudia Giovanni, Douglas Grindlay, Matthew Helbert, John Holmes, Jackie Kervick, Suzannah Kinsella, Maggie Mcphee, Carrie Newlands, Viktorija Petraitiene, Jonathan Pollock, Angelika Razzaque, Agata Rembielak, Jonathan Rodrigues, David Snow, Diane Thompson, Ayath Ullah, David Veitch, Aaron Wernham, Carrie Wingfield, Stela Ziaj
Journal: British Journal of Dermatology (2022)

The incidence of skin cancer is increasing and surgery is the mainstay of management. The James Lind Alliance (JLA) priority setting partnership (PSP) was designed to address research uncertainties in skin cancer surgery. We report the outcome and top ten research priorities from the JLA PSP in skin cancer surgery.
Semi-virtual patch testing: the future?
Authors: Rosie Vincent, Emma Ormerod, Charlotte E Gollins, Nabina Rai, Karen Conduit-Turner, Aparna Sinha, Jane Sansom
Journal: British Journal of Dermatology (2022)

A review of 181 patients that underwent ‘semi-virtual’ patch testing using virtual day 2 readings. Results highlight that most patients are able to remove patches and take high quality images via smart phone technology, with very limited adverse clinical impact. A notable reduction in travel was required, with subsequent positive environmental impacts.